Ventilator-associated complications in patients with ESBLE infections

EJRC Article Review

Extended-spectrum b-lactamase producing Enterobacteriaceae (ESBLE) colonise a growing proportion of critically ill patients in the intensive care unit (ICU)[1]. ESBLE colonisation is an established risk factor for subsequent infections [2]. Although guidelines suggest to consider the colonisation status of patients to adjust empirical treatment in case of suspected nosocomial infections, some evidence suggests that this approach may increase carbapenem consumption and the dissemination of carbapenem-resistant Gram-negative bacteria [3]. Quite recently, the Centre for Disease Control and Prevention (CDC) defined infection-related ventilator-associated complications (IVAC) as a subset of ventilator associated conditions with systemic inflammatory response suggesting a new infection and leading to either the start of a new antibiotic treatment or the broadening of spectrum of an ongoing one [4].

Barbier and colleagues conducted an inception cohort study from the prospective French multicentre OUTCOMEREA database (17 ICUs, 1997-2015), which aimed to evaluate the epidemiology, related carbapenem consumption and clinical significance of IVAC episodes in mechanically ventilated (MV) ICU patients colonised by ESBLE [5]. All ESBLE carriers (systematic rectal swabbing, urinary or superficial surgical site colonisation) receiving MV for more than 2 days, no previous episode of ESBLE VAP and ≥ 1 IVAC episode after documentation of colonisation were included.

A total 576 IVAC episodes were analysed; 318 ESBLE carriers were included in the cohort. The 63.7% (361) of IVACs was not attributable to a documented ICU-acquired infection, the 21.5% (124) was related to > 1 non-VAP ICU-acquired infection, the 12.7% (73) was related to non-ESBLE VAP, while only the 3% (18) was related to ESBLE VAP. Overall, only 43 IVACs (7.5%) were associated with > 1 ICU-acquired ESBLE infection. Regarding the risk for ESBL infection, carbapenem exposure within 3 days preceding IVAC was identified as the only independent predictor (protective effect – OR 0.2, 95% CI 0.05-0.6, P <0.01). A new carbapenem-based treatment was started in the 29.6% of IVACs (94). Interestingly, the carbapenem use was similar in IVACs related to ESBLE VAP and non-ESBLE VAP (p=ns). The proportion of patients who died during an IVAC episode (overall, 18%) and the median subsequent MV duration (overall 3 (6-10)) were higher in VAP-related IVACs, but there was no difference between ESBLE and non-ESBLE VAP. 

Strengths

• Multicentre design, large number of patients, prospectively collected data, accurate statistical analysis.

Main Limitations

• No assessment of the ecological impact of carbapenem misuse in non-ESBLE IVACs.
• No comparison between the empirical antibiotic regimens for IVACs to a matched cohort non-colonised with ESBLE.
• The impact of ESBLE lower respiratory colonisation (LRT) on IVAC causes was not explored as no LRT surveillance cultures were performed.
• All ICU-acquired infections were microbiologically documented using strict thresholds. Therefore, misclassification of a number of IVACs as non-infection related cannot be excluded in cases of sampling after antibiotics were already started (and thus over-estimation of the carbapenem protective effect cannot be ruled out).

Take-home messages

• The majority of IVAC episodes in ESBLE carriers were not attributable to documented infection and were unrelated to colonisation status. However, they ESBLE colonisation acted as strong drivers for carbapenem use.
• ESBLE infections were hardly predictable. Thus, the development of novel diagnostic algorithms and validation of carbapenem-sparing regimens is crucial for diagnosis optimisation and reduction of selective pressure for carbapenem resistance in ESBLE carriers with IVAC.

Review by Dr Andrea Cortegiani and Dr Despoina Koulenti on behalf of the Working Group on Pneumonia.

References

1. Bassetti M, De Waele JJ, Eggimann P, et al (2015) Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria. Intensive Care Med 41:776–795. doi: 10.1007/s00134-015-3719-z
2. Detsis M, Karanika S, Mylonakis E (2017) ICU Acquisition Rate, Risk Factors, and Clinical Significance of Digestive Tract Colonisation With Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae: A Systematic Review and Meta-Analysis. Crit Care Med 45:705–714. doi: 10.1097/CCM.0000000000002253
3. Bretonniere C, Leone M, Milesi C, et al (2015) Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric). Intensive Care Med 41:1181–1196. doi: 10.1007/s00134-015-3853-7
4. Magill SS, Klompas M, Balk R, et al (2013) Developing a New, National Approach to Surveillance for Ventilator-Associated Events: Executive Summary. Clin Infect Dis 57:1742–1746.
5. Barbier F, Bailly S, Schwebel C, et al (2018) Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum beta-lactamase-producing Enterobacteriaceae. Intensive Care Med. doi: 10.1007/s00134-018-5154-4